Enhancing protein fold determination by exploring the complementary information of chemical cross-linking and coevolutionary signals

Autor(es)

dos Santos, Ricardo N. ^{[1, 2]} ; Ferrari, Allan J. R. ^[1] ; de Jesus, Hugo C. R. ^[1] ; Gozzo, Fabio C. ^[1] ; Morcos, Faruck ^[3] ; Martinez, Leandro ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Ctr Computat Engn & Sci, BR-13083970 Campinas, SP - Brazil

^[3] Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75080 - USA

• Tipo de documento: Artigo Científico
• Fonte: Bioinformatics; v. 34, n. 13, p. 2201-2208, JUL 1 2018.
• Citações Web of Science: 6

Resumo

Motivation: Elucidation of protein native states from amino acid sequences is a primary computational challenge. Modern computational and experimental methodologies, such as molecular coevolution and chemical cross-linking mass-spectrometry allowed protein structural characterization to previously intangible systems. Despite several independent successful examples, data from these distinct methodologies have not been systematically studied in conjunction. One challenge of structural inference using coevolution is that it is limited to sequence fragments within a conserved and unique domain for which sufficient sequence datasets are available. Therefore, coupling coevolutionary data with complimentary distance constraints from orthogonal sources can provide additional precision to structure prediction methodologies. Results: In this work, we present a methodology to combine residue interaction data obtained from coevolutionary information and cross-linking/mass spectrometry distance constraints in order to identify functional states of proteins. Using a combination of structure-based models (SBMs) with optimized Gaussian-like potentials, secondary structure estimation and simulated annealing molecular dynamics, we provide an automated methodology to integrate constraint data from diverse sources in order to elucidate the native conformation of full protein systems with distinct complexity and structural topologies. We show that cross-linking mass spectrometry constraints improve the structure predictions obtained from SBMs and coevolution signals, and that the constraints obtained by each method have a useful degree of complementarity that promotes enhanced fold estimates. (AU)

• Processo FAPESP: 13/08293-7 - CECC - Centro de Engenharia e Ciências Computacionais
• Beneficiário: Munir Salomao Skaf
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 13/05475-7 - Métodos computacionais de otimização
• Beneficiário: Sandra Augusta Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/13195-2 - Modelagem da estrutura de proteínas e de complexos protéicos usando dados de espectrometria de massas
• Beneficiário: Allan Jhonathan Ramos Ferrari
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/17264-3 - Novas fronteiras em proteômica estrutural: caracterizando estruturas de proteínas e complexos proteicos por espectrometria de massas
• Beneficiário: Fabio Cesar Gozzo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/13667-9 - Estudos de sistemas multiméricos de proteínas através de cross-linking, espectrometria de massas e modelagem molecular
• Beneficiário: Ricardo Nascimento dos Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/16947-9 - Estrutura, dinâmica e função em proteínas: simulação computacional e desenvolvimento de algoritmos
• Beneficiário: Leandro Martinez
• Modalidade de apoio: Auxílio à Pesquisa - Regular